WS1-4 - Everolimus

Abstract

Everolimus is an mTOR inhibitor which shows activity across the cancers from various origins. Everolimus is currently approved in Japan for breast cancer, renal cancer, pancreas neuroendocrine tumor (pNET), subependymal giant cell astrocytoma (SEGA), renal angiomyolipoma associated with tuberous sclerosis complex. In breast cancer, efficacy of everolimus has been explored mainly in patients with hormone-receptor positive or HER2-positive breast cancer. Randomized phase III trial BORELO-2 compared everolimus in combination with exemestane plus placebo with exemestane in patients with hormone-receptor positive breast cancer who were refractory to non-steroidal aromatase inhibitor. Progression-free survival (PFS) was significantly longer in everolimus arm (median PFS 6.9 months vs 2.8 months; hazard ratio (HR) 0.43; p < 0.001). However, the difference in overall survival was not significant (HR 0.89; p = 0.14). In the BOLERO-1 and BOLERO-3 study, everolimus was explored in patients with HER2-positive breast cancer. Unfortunately everolimus failed to demonstrate efficacy (BOLERO-1) or only showed limited efficacy (BOLERO-3). Common severe adverse events of everolimus reported in BOLERO-2 trial were stomatitis (8%), anemia (6%), dyspnea (4%), hyperglycemia (4%), fatigue (4%), and pneumonitis (3%). Stomatitis is one of the most common adverse events and impairs quality of life (QOL) in patients. Prophylactic treatment and early recognition of stomatitis is important. Pneumonitis is a class effect of mTOR inhibitors. Current evidence suggests that pneumonitis may be immunologically mediated. Therapy should be interrupted and corticosteroid treatment initiated if a patient's symptoms are moderate to severe. Everolimus is generally well tolerated, however it is important to consider risk benefit balance as everolimus is related to some adverse events which can significantly impair QOL in patients.